摘要
Understanding the atomic level interactions and the resulting structural characteristics is required for developing beta-cyclodextrin (beta CD) derivatives for pharmaceutical and other applications. The effect of four different solvents on the structures of the native beta CD and its hydrophilic (methylated beta CD; ME beta CD and hydroxypropyl beta CD; HP beta CD) and hydrophobic derivatives (ethylated beta CD; ET beta CD) was explored using molecular dynamics (MD) simulations and solvation free energy calculations. The native beta CD, 2-ME beta CD, 6-ME beta CD, 2,6-DM beta CD, 2,3,6-TM beta CD, 6-HP beta CD, 2,6-HP beta CD and 2,6-ET beta CD in non-polar solvents (cyclohexane; CHX and octane; OCT) were stably formed in a symmetric cyclic cavity shape through their intramolecular hydrogen bonds. In contrast, beta CDs in polar solvents (methanol; MeOH and water; WAT) exhibited large structural changes and fluctuations leading to significant deformations of their cavities. Hydrogen bonding with polar solvents was found to be one of the major contributors to this behavior: solvent-beta CD hydrogen bonding strongly competes with intramolecular bonding leading to significant changes in the structural stability of beta CDs. An exception to this is the hydrophobic 2,6-ET beta CD which retained its spherical cavity in all solvents. Based on this, it is proposed that the 2,6-ET beta CD can act as a sustained release drug carrier.
- 出版日期2017-9-21